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European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy
  1. Kyriaki Tzogani1,
  2. Beatriz Florez2,
  3. Greg Markey2,
  4. Mariapaola Caleno3,
  5. Odoardo Maria Olimpieri3,
  6. Daniela Melchiorri4,
  7. Doris Johanna Hovgaard5,
  8. Sinan Bardakci Sarac5,
  9. Karri Penttilä6,
  10. Tuomo Lapveteläinen6,
  11. Tomas Salmonson7,
  12. Jonas Bergh8,
  13. Christian Gisselbrecht9,
  14. Francesco Pignatti1
  1. 1 European Medicines Agency, Amsterdam, The Netherlands
  2. 2 MHRA, London, UK
  3. 3 AIFA, Roma, Italy
  4. 4 Dip. Physiology and Pharmacology, V. Erspamer, University of Rome La Sapienza, Roma, Italy
  5. 5 Laegemiddelstyrelsen, Kobenhavn, Denmark
  6. 6 Finnish Medicines Agency Fimea, Helsinki, Finland
  7. 7 Lakemedelsverket, Uppsala, Sweden
  8. 8 Radiumhemmet Microbiology and Tumorbiology Center, Karolinska University Hospital, Stockholm, Sweden
  9. 9 Institut d'Hématologie, Hôpital Saint Louis Paris Diderot Université, Hospital Saint-Louis, Paris, France
  1. Correspondence to Kyriaki Tzogani; kyriaki.tzogani{at}ema.europa.eu

Abstract

On 21 November 2016, the European Commission issued a marketing authorisation valid throughout the European Union for ixazomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Ixazomib was evaluated in one, randomised, double-blind, phase III study comparing ixazomib plus lenalidomide and dexamethasone (n=360; ixazomib arm) versus placebo plus lenalidomide and dexamethasone (n=362; placebo arm) in adult patients with relapsed and/or refractory multiple myeloma who had received at least one prior therapy. The median progression-free survival (PFS) in the intent-to-treat population was 20.6 months in patients treated with ixazomib compared with 14.7 months for patients in the placebo arm (stratified HR=0.742, 95% CI 0.587 to 0.939, stratified p-value=0.012). The most frequently reported adverse reactions (≥20%) within the ixazomib and placebo arms were diarrhoea (42% vs 36%), constipation (34% vs 25%), thrombocytopaenia (28% vs 14%), peripheral neuropathy (28% vs 21%), nausea (26% vs 21%), peripheral oedema (25% vs 18%), vomiting (22% vs 11%) and back pain (21% vs 16%). The scientific review concluded that the gain in PFS of 5.9 months observed with ixazomib was considered clinically meaningful. Concerning the possible uncertainty about the magnitude of the effect, this uncertainty was acceptable given the favourable toxicity profile, and considering that ixazomib is the first agent to allow oral triple combination therapy in this patient population which represents a therapeutic innovation in terms of convenience for patients. Therefore, the benefit–risk for ixazomib in combination with lenalidomide and dexamethasone was considered positive, although the efficacy evidence was not as comprehensive as normally required.

  • ixazomib
  • multiple myeloma
  • EMA
  • European Medicines Agency

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Footnotes

  • Contributors Data analysis and interpretation: BF, GM, MC, OO, DM, Dh, SBS, KP, TL. Manuscript writing: KT, BF, GM, MC, OO, DM, DH, SBS, KP, TL, FP. Final approval of manuscript: KT, BF, GM, MC, OO, DM, DH, SBS, KP, TL, TS, JB, CG, FP.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Disclaimer This publication is based on the scientific review of the application leading to approval of ixazomib in the EU. The detailed scientific assessment report and product information for this product are available on the European Medicines Agency website (http://www.ema.europa.eu). The authors of this paper remain solely responsible for the opinions expressed in this publication.

  • Competing interests Jonas Bergh:Research grants for academic clinical studies/ molecular marker spin-off to Karolinska University Hospital and/or Karolinska Institutet from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi Aventis, no personal payments.Honoraria from UpToDate for the chapter on “Prognostic and Therapy Predictive factors" for early breast cancer to Asklepios Medicin HB.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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